PN Group Research Articles

Prognostic value of isolated tumor cells and micrometastasis of lymph nodes in invasive urinary bladder cancer.

The prognostic significance of nodal micrometastasis and isolated tumor cells (ITC) in urinary bladder cancer (UBC) is unknown. We aimed to evaluate the prevalence, clinical impact, and clinicopathological characteristics of nodal micrometastasis and ITC in UBC. A total of 124 patients with UBC undergoing surgery were investigated. Detection of micrometastasis and ITC was performed using pancytokeratin immunohistochemistry (IHC). Histopathologic and clinical findings were correlated with patients' outcome. IHC detected nodal micrometastasis and ITC (pNmi group) in 12.9% (13/101) of originally node-negative patients and in 26.1% (6/23) of originally node-positive patients (pN+ group). The remaining 88 were truly node-negative patients (pN0 group). After IHC, all 13 patients in the pNmi group were upstaged from pN0 to pN1-2 and one patient in the pN+ group was changed from pN1 to pN2. Nodal micrometastasis and ITC were significantly associated with mixed urothelial carcinoma (UC) (p = 0.002), UC with discohesive pattern (p = 0.006), glandular differentiation (p = 0.043), lymphovascular invasion (p = 0.009), and budding-like tumor cell clusters (p = 0.002). The pNmi group had significantly worse cancer-specific survival than the pN0 group in univariate (p = 0.004) and multivariate (p = 0.040) analysis. IHC frequently identified nodal micrometastasis and ITC in originally node-negative UBC patients on routine pathological examination. Nodal micrometastasis and ITC were independently associated with cancer-related mortality in UBC. IHC might be selectively used to detect micrometastasis and ITC in UBC having specific pathological features.

A single-blinded, randomized, parallel intervention to evaluate genetics and omics-based personalized nutrition in general population via an e-commerce tool: The PREVENTOMICS e-commerce study

BackgroundPersonalized nutrition (PN) has been proposed as a strategy to increase the effectiveness of dietary recommendations and ultimately improve health status. ObjectivesWe aimed to assess whether including omics-based PN in an e-commerce tool improves dietary behavior and metabolic profile in general population. MethodsA 21-wk parallel, single-blinded, randomized intervention involved 193 adults assigned to a control group following Mediterranean diet recommendations (n = 57, completers = 36), PN (n = 70, completers = 45), or personalized plan (PP, n = 68, completers = 53) integrating a behavioral change program with PN recommendations. The intervention used metabolomics, proteomics, and genetic data to assist participants in creating personalized shopping lists in a simulated e-commerce retailer portal. The primary outcome was the Mediterranean diet adherence screener (MEDAS) score; secondary outcomes included biometric and metabolic markers and dietary habits. ResultsVolunteers were categorized with a scoring system based on biomarkers of lipid, carbohydrate metabolism, inflammation, oxidative stress, and microbiota, and dietary recommendations delivered accordingly in the PN and PP groups. The intervention significantly increased MEDAS scores in all volunteers (control—3 points; 95% confidence interval [CI]: 2.2, 3.8; PN—2.7 points; 95% CI: 2.0, 3.3; and PP—2.8 points; 95% CI: 2.1, 3.4; q < 0.001). No significant differences were observed in dietary habits or health parameters between PN and control groups after adjustment for multiple comparisons. Nevertheless, personalized recommendations significantly (false discovery rate < 0.05) and selectively enhanced the scores calculated with biomarkers of carbohydrate metabolism (β: −0.37; 95% CI: −0.56, −0.18), oxidative stress (β: −0.37; 95% CI: −0.60, −0.15), microbiota (β: −0.38; 95% CI: −0.63, −0.15), and inflammation (β: −0.78; 95% CI: −1.24, −0.31) compared with control diet. ConclusionsIntegration of personalized strategies within an e-commerce–like tool did not enhance adherence to Mediterranean diet or improved health markers compared with general recommendations. The metabotyping approach showed promising results and more research is guaranteed to further promote its application in PN.This trial was registered at clinicaltrials.gov as NCT04641559 (https://clinicaltrials.gov/study/NCT04641559?cond=NCT04641559&rank=1).

Functional connectivity associated with attention networks differs among subgroups of fibromyalgia patients: an observational case–control study

Fibromyalgia is a heterogenous chronic pain disorder diagnosed by symptom-based criteria. The aim of this study was to clarify different pathophysiological characteristics between subgroups of patients with fibromyalgia. We identified subgroups with distinct pain thresholds: those with a low pressure pain threshold (PL; 16 patients) and those with a normal pressure pain threshold (PN; 15 patients). Both groups experienced severe pain. We performed resting-state functional MRI analysis and detected 11 functional connectivity pairs among all 164 ROIs with distinct difference between the two groups (p < 0.001). The most distinctive one was that the PN group had significantly higher functional connectivity between the secondary somatosensory area and the dorsal attention network (p < 0.0001). Then, we investigated the transmission pathway of pain stimuli. Functional connectivity of the thalamus to the insular cortex was significantly higher in the PL group (p < 0.01 – 0.05). These results suggest that endogenous pain driven by top-down signals via the dorsal attention network may contribute to pain sensation in a subgroup of fibromyalgia patients with a normal pain threshold. Besides, external pain driven by bottom-up signals via the spinothalamic tract may contribute to pain sensations in another group of patients with a low pain threshold. Trial registration: UMIN000037712.

Fracture of the patella involving inferior pole is associated with postoperative patella baja - A retrospective multicenter study

BackgroundThe patella fracture involving of inferior pole fractures (IPF) may be associated with patella baja, However, the clinical impact of this condition remains unclear. This study aims to clarify 1) the incidence of patella baja following patellar fracture surgery, 2) the associated clinical outcomes with and without the presence of patella baja, and 3) the potential correlation between the detection of IPF on CT and the occurrence of patella baja. MethodsWe conducted a retrospective multicenter study involving 251 patients who underwent surgical treatment for patellar fractures. Patients were divided into the patella baja (PB; n = 49) group and patella norma (PN; n = 202) group. Data collected included demographics, radiographic findings, surgical details, and postoperative complications. We compared these items between PB group and PN group. Logistic regression analyses were used to identify risk factors for patella baja. ResultsImmediately following surgery, 36 (14.3%) patients presented with patella baja which increased to 49 cases (19.5%) at six months postoperatively. There is no statistically significant difference in the demographics, surgical details, clinical outcomes and complication between PB group and PN group. While, in the radiographical assessment, the prevalence of IPF on CT scan in the patella baja group was significantly higher than that in the patella norma group. By logistic regression analysis, IPFP on CT was identified as an independent risk factor for patella baja. (odds ratio 2.11, 95% confidence interval: 1.03–4.33, p = 0.042). ConclusionIn patients with patellar fractures, the incidence of patella baja increased from 14.3% immediately post-surgery to 19.5% at the six-month check-up. No significant differences were observed in clinical outcomes between the patella baja group and the norma group. The patella fracture involving IPF on CT emerged as a predictive factor for patella baja.

Comprehensive Long-Read Sequencing Analysis Discloses the Transcriptome Features of Papillary Thyroid Microcarcinoma.

Papillary thyroid microcarcinoma (PTMC) is the most common type of thyroid cancer. It has been shown that lymph node metastasis is associated with poor prognosis in patients with PTMC. We aim to characterize the PTMC transcriptome landscape and identify the candidate transcripts that are associated with lateral neck lymph node metastasis of PTMC. We performed full-length transcriptome sequencing in 64 PTMC samples. Standard bioinformatic pipelines were applied to characterize and annotate the full-length expression profiles of 2 PTMC subtypes. Functional open reading frame (ORF) annotation of the known and novel transcripts were predicted by HMMER, DeepLoc, and DeepTMHMM tools. Candidate transcripts associated with the pN1b subtype were identified after transcript quantification and differential gene expression analyses. We found that skipping exons accounted for the more than 27.82% of the alternative splicing events. At least 42.56% of the discovered transcripts were novel isoforms of annotated genes. A total of 39 193 ORFs in novel transcripts and 18 596 ORFs in known transcripts were identified. Distribution patterns of the characterized transcripts in functional domain, subcellular localization, and transmembrane structure were predicted. In total, 1033 and 1204 differentially expressed genes were identified in the pN0 and pN1b groups, respectively. Moreover, novel isoforms of FRMD3, NOD1, and SHROOM4 were highlighted for their association with pN1b subtype. Our data provided the global transcriptome landscape of PTMC and also revealed the novel isoforms that associated with PTMC aggressiveness.

953 Outcomes of Partial Nephrectomy for pT3a Renal Cell Cancer Over 20 Years at a Single Centre

Abstract Aim There is limited information on outcomes of pT3a RCC treated with PN. Retrospective studies of cT1/2 upstaged to pT3a treated with RN vs PN show contradictory results. Method Retrospective analysis of all pT3a renal tumours removed by either RN or PN between 2000-2020 at a single centre performed by 6 surgeons with a median follow up period of 4 years. Results 186 cases of pT3a RCC were treated with RN and 78 with PN. There was CT suspicion of T3a disease in 1 PN and 6 RN cases. The mean tumour size in PN vs RN was 4.5cm vs. 8cm. Preoperative and postoperative eGFR were similar between RN and PN groups with a smaller drop in eGFR from preop to post op in the PN vs RN group (16 vs 20ml/min) The number of patients who went on to have renal replacement therapy for end stage renal failure was 6 in the RN group and 2 in the PN group. At median 4 years follow up, 86% of PN patient were alive vs 93% who had RN. Of the patients who had died 5.6% were due to renal cancer in the PN group vs 8.6% in the RN group. The rate of any recurrence or spread of renal cancer detected at follow up was 21% in the PN group and 38% in the RN group. Conclusions This case series suggests PN for pT3a tumours is a reasonable option for patients who have strong indications for nephron sparing surgery.

Clinicopathological features and prognostic factors of salivary gland myoepithelial carcinoma: institutional experience of 42 cases

Myoepithelial carcinoma (MECA) is a rare type of carcinoma for which the clinicopathological features and prognostic factors have not yet been fully clarified. A retrospective study of 42 patients diagnosed with salivary gland MECA was performed, focusing on the clinicopathological features and prognostic factors. Of the 42 patients, 20 died of cancer, 20 lived without tumour, one lived with distant metastasis, and one was lost to follow-up. Overall, 69.0% had tumour recurrence, 16.7% had cervical nodal metastasis, and 21.4% had distant metastasis. The 5-year overall survival rate was 70.2%. Kaplan–Meier analysis revealed that patients with pathological positive lymph nodes (pN+), multiple recurrences of tumour, and higher histological grade had worse overall survival. Multivariate Cox analysis indicated pN+ and higher histological grade to be independent predictors of decreased survival. The 5-year overall survival rate in the pN0 group was 87.5%, while that in the pN+ group was 28.6%. In conclusion, myoepithelial carcinoma can be defined as a tumour with a high incidence of recurrence and poor prognosis, especially in pN+ patients. Pathological positive lymph nodes and histological grade may serve as predictors of survival.

Is tumor diameter a risk factor for occult N1 metastasis in patients with peripheral non-small cell lung cancer which is smaller than 3 cm?

The optimum treatment option is surgery for clinical early stage non-small cell lung cancer. Despite all non-invasive and invasive staging effort, occult lymph-node metastasis can be detected in pathological staging. Here, we investigated whether there was any correlation between tumor diameter and occult lymph-node metastasis in N1 stations. Data of patient with non-small cell lung cancer clinical stage 1A were reviewed retrospectively. Those with tumor diameter smaller than 3cm and pN0-pN1 in pathological staging were included in the study. Overall survival (OS) was calculated by Kaplan-Meier and survival differences between pN0 and pN1 groups were investigated by Log-Rank methods. Cut-off value of tumor diameter for lymph-node metastasis was investigated by Receiver-Operating Characteristics test. Significance between pN0-pN1 and other categorical groups was investigated with Pearson Chi-square or Fisher's exact tests. A total of 257 patients meet to criteria included in the study. Fifty-five (21.4%) of the patients were females. The mean age was 62.7 ± 8.5 and median tumor diameter was 20mm (Range: 2-30mm). We detected occult lymph-node metastasis at the N1 stations (pN1) in 33 patients (12.8%) in histopathological examination of resected specimens and lymph-node dissection materials. The cut-off value of tumor diameter was calculated as 21.5mm for occult lymph-node metastasis by Receiver-Operating Characteristics analysis (Area Under Curved: 70.1%, p = 0.004). There was a significant correlation between pN1 positivity and high tumor diameter (p = 0.02). However, we did not find a correlation between the lymph-node metastasis and age, gender, tumor histopathology, tumor localization, and visceral pleural invasion. Tumor diameter may be an indicator for occult lymph-node metastasis in patients with clinical stage-1A non-small cell lung cancer. This result should be considered in patient with mass which larger than 21.5mm and planned stereotactic body radiotherapy instead of surgery.

A randomized controlled trial for comparing efficacy and safety between intraarticular polynucleotide and hyaluronic acid for knee osteoarthritis treatment

Although the use of intra-articular polynucleotide (IA PN) injection as a viscosupplement for knee osteoarthritis (OA) treatment has been proposed, its efficacy and safety compared to high molecular weight hyaluronic acid (HMWHA) injection has not yet been established. The present double-blind, multicenter, randomized controlled trial aimed to investigate the efficacy and safety of IA PN injection compared to IA HMWHA injection. A total of 60 patients (15 men, 45 women, 64.5 ± 7.5 years) with knee OA (Kellgren–Lawrence grade 1–4) were randomly allocated to each group. All patients were given three IA injections of PN (n = 30) or HMWHA (n = 30) at intervals of 1 week. The primary endpoint was the change rate in weight-bearing pain (WBP) 16 weeks from the baseline. The secondary endpoint included multiple measurements: the change rate in WBP rate at 8 weeks; the change rate in pain level at rest and during walking at 8 and 16 weeks; the Korean-Western Ontario and McMaster University Osteoarthritis index; the Euro-Quality of Life-5 Dimension; Clinical Global Impression, Patient Global Impression at 8 and16 weeks, and total consumption of rescue medicine. The mean change rate in the WBP at 16 weeks from the baseline was − 54.0 ± 38.1% in the IA PN group and − 42.8 (± 35.8%) in the IA HMWHA group, and there was no significant difference between the two groups (p = 0.296). All secondary endpoints related with pain and functional outcome also showed no significant difference between the two groups. Pain at the injection site and swelling were reported as adverse events, and the incidence was similar between the two groups. IA PN showed comparable efficacy and safety to IA HMWHA at 3 times injection with an interval of 1 week. IA PN can be useful alternative to IA HMWHA for the treatment of knee OA.

A combination of circulating tumor cell (CTC) and cancer stem cell (CSC) markers to predict the prognosis of breast cancer.

e13007 Background: CTCs are tumor cells that shed from either primary tumor or metastatic foci and can provide more information about the tumor's biological entity than circulating tumor DNA (ctDNA), or exosomes do. The current FDA-approved CTC assay misses the CSC phenotypes, which are pivotal in driving tumorigenesis, metastasis, resistance to treatment, and cancer recurrence. Therefore, we combine CTC and CSC markers to determine the prognosis. We hypothesized that the CSC markers on CTC correlate with poorer outcomes. Methods: Peripheral blood samples of qualified breast cancer patients were collected at diagnosis and every 6 months during follow-up. EpCAM, MUC-1, and HER2 are used as CTC markers, while TWIST, AKT, PI3K, and ALDH-1 are used to detect CSC. According to the expression level of the above markers, patients were categorized into four groups: NN negative with both CTC and CSC markers, NP expressing CSC markers, PN expressing CTC markers, and PP positive with both CTC and CSC markers. The progression-free survival (PFS) and overall survival (OS) of all four groups were calculated by Kaplan-Meier model from the date of surgery until the disease progression and death/the last follow-up of the patients, respectively. Results: We screened 100 patients aged 18 years or older with confirmed stage II to stage IV breast cancer and selected 81 patients for the study. Fifteen patients dropped out of the study due to loss of follow-up or incomplete clinical information leaving 66 evaluable patients. There are 55 Caucasians (83%), 5 African Americans (7.5%), 5 Hispanics (7.5%), and 1 Asian (1.5%). The median age of the patients is 52.5 years old (29-81), and the median follow-up is 22.6 months (2.5-65). Most patients have stage III disease (60 and 91%) followed by 4 stage IV (6%) and 2 Stage II (3%). The median time between the first sample date and surgery is 172 days (-148 to 270). The NN group has the most patients (41 and 62%) compared to NP group (16 and 24%) and PN group (6 and 9%). The PP group has the least number of patients (2 and 3%) and is not observed in patients with positive hormonal receptors (HR). The PN group has a higher ratio of HR-HER2+ patients than NP group does. The HR and HER2 statuses were checked in the four groups. Interestingly, the NN and NP groups are mostly HR+HER2- patients, while the PN group is mainly HR- patients regardless of the HER2 status. The PP group only has HR- patients. The PFS curves start to flatten at 12 months and separate among the four groups, with the highest PFS percentage in the NP (81.2%) and NN (77.8%) followed by the PN (62.5%) and PP (50%) group. The OS percentage is 70% in NN, 66% in PN, 60% in NP, and 50% in PP, similar to the PFS pattern. Conclusions: Checking both CTC and CSC markers help triage the prognosis of breast cancer patients. CTC and CSC markers observed in breast cancer patients with different HR or HER2 status can be further investigated for potential correlations.

Polystyrene nanoplastics exacerbated Pb-induced liver toxicity in mice.

Nanoplastics are widely distributed in the environment and can adsorb heavy metals, which poses a potential threat to human health through food chain. It is necessary to assess the combined toxicity of nanoplastics and heavy metals. The adverse effect of Pb and nanoplastics on liver, single or in combination, was evaluated in this study. The results showed that the Pb content in co-exposure group of nanoplastics and Pb (PN group) was higher than the group exposed to Pb alone (Pb group). And more severe inflammatory infiltration was observed in liver sections of PN group. The level of inflammatory cytokines and malondialdehyde were increased, while the superoxide dismutase activity was decreased in liver tissues of PN group. Moreover, the gene expression level of nuclear factor-erythroid 2-related factor 2, nicotinamide adenine dinucleotide phosphate:quinine oxidoreductase 1 and catalase, which is related to antioxidation, was downregulated. And the expression level of cleaved-Caspase9 and cleaved-Caspase3 were increased. However, with the supplementation of oxidative stress inhibitor N-Acetyl-L-cysteine, liver damage shown in PN group was evidently alleviated. In summary, nanoplastics evidently exacerbated the deposition of Pb in liver and potentially aggravated the Pb-induced liver toxicity by activating oxidative stress.

Oncologic safety of the pedicled submental island flap for reconstruction in oral tongue squamous cell carcinoma: An analysis of 101 cases

ObjectiveTo evaluate whether the pedicle submental island flap (SIF) can be safely used in the oral tongue squamous cell carcinoma (OTSCC) patients with pathologically node-positive (pN+) neck, especially pN+ at level I. MethodsRetrospectively, 101 OTSCC patients with SIF reconstruction were enrolled. Oncological outcomes included the total locoregional recurrence, the SIF related locoregional recurrence (SRLR) which referred to the local recurrence at flap and ipsilateral neck recurrence at level I, recurrence free survival (RFS), overall survival (OS), and disease specific survival (DSS). ResultsSixty-one patients were pathologically node-negative (pN0) and 40 were pN+. Thirteen patients experienced locoregional recurrence, of which 5 had a SRLR. The pN+ group had a significantly higher locoregional recurrence rate, lower 5-year RFS, OS and DSS than pN0 group (P < 0.05). Patients with pN0 had a significantly higher neck RFS when compared to those with pN+ either at level I (P = 0.005) or at other levels (P < 0.001). However, the neck RFS was similar between the two subgroups of pN+ (P = 0.550). Especially, patients with pN+ at level I had a significantly higher SRLR rate (P = 0.006) compared to those with pN0 at level I. Multivariate analysis showed that pN+ was an unfavorable factor for tumor recurrence and OS. ConclusionOur data did not support the use of SIF in OTSCC patients with pN+ neck at level I due to an significantly increased SRLR rate compared to those with pN0 neck at level I.

Evaluation of the post-implantation development of mouse embryos derived from round spermatid injection

Round spermatid injection (ROSI), one of the assistant reproductive technologies, was used to treat partial infertility patients suffering from non-obstructive azoospermia. However, the development efficiency and birth rate of ROSI embryos are extremely low, and it is urgent to investigate the underlying mechanisms of low efficiency to improve the clinical application of ROSI technology. Here, we analyzed and compared the genome stability of the mouse blastocyst and the post-implantation development between ROSI and ICSI embryos. We first sequenced the genome of blastocysts from mouse ROSI embryos that can correctly form male and female pronuclei (2 PN) and found that the genomes of 7 blastocysts were normal. Furthermore, the implantation rate of ROSI 2 PN embryos on embryonic day 7.5 is similar to that of ICSI embryos, and at this time, 37.50% (9/24) of deciduas have no normal gestational sac. The proportion of embryos that survived to embryonic day 11.5 in the ROSI 2 PN group, ROSI non-2 PN group, parthenogenesis group, and ICSI 2 PN group was 51.61%, 7.14%, 0.00%, and 55.00%, respectively. And two smaller fetuses were found in the ROSI 2 PN group, which is not found in the other three groups. In addition, the physiological indexes, including fetus and placenta weight, sex ratio, growth rate, and the natural breeding ability for the offspring obtained from mouse ROSI, were evaluated; ROSI mice exhibited no obvious defect or abnormality and implied that the progeny were safe. Our results provided new evidence to promote the clinical application of ROSI technology.

Early enteral versus early parenteral nutrition in critically ill patients with respiratory distress: a case–control study

BackgroundNutritional support is essential as enteral or parenteral nutrition to reduce catabolism, to lower the complications rate, and to improve outcomes in critically ill patients.ResultsThe median, range age of the cohort was (median 10, range 6–18.8 months). One-hundred thirteen (62.8%) were males, and 67 (37.2%) were females. The higher frequency of sepsis, ventilator-acquired pneumonia (VAP), and mortality founded in the group received PN. Frequency of sepsis was 15 (16.7%), VAP was 5 (5.6%), and the mortality rate was 11.1% in EN group, while frequency of sepsis was 37 (41.1%), VAP was 23 (25.6%), and the mortality rate was 27.8% in PN group (P = 0.001, 0.001, 0.01, respectively). Median of weight gain on the EN group was 0.17 kg at 2nd week which was more than those in PN group (P = 0.001). The mean ± SD time for reaching the caloric target for those receiving early EN was 4.0 ± 1.9 days which is earlier than that of PN group (6.2 ± 1.7 days) (P = 0.001). There is no significant difference between both groups as regard pediatric intensive care unit (PICU) stay length and mechanical ventilation stay length.ConclusionEarly EN remains the preferred route for nutrient delivery as the PN route was accompanied by a lot of complication such as sepsis, VAP, and high mortality rate.

Histopathological and ultra-structural investigation of the damaging effects of hypoinsulinemia, hyper glycaemia and oxidative stress caused by parenteral nutrition combined with fasting on the small intestine of rabbits

Background and study aimsParenteral nutrition (PN) is a life-saving practice when the use of the gastrointestinal tract is not appropriate. Despite its great benefits, however, PN may cause several complications. In this study, we conducted histopathological and ultra-structural examinations of the effect of PN combined with starvation on the small intestines of rabbits. Materials and methodsRabbits were divided into four groups. A fasting + PN group was left completely unfed and received all its daily required energy by PN through an intravenous central catheter. An oral feeding + PN group received half the necessary daily calories by oral feeding and the other half through PN. A semi-starvation group received only half the necessary daily calories by oral feeding and no PN. The fourth group, serving as a control, was supplied with its entire daily energy requirements through oral feeding. After 10 days, the rabbits were euthanized. Blood and small intestine tissue samples were collected from all groups. Blood samples were biochemically analysed, and tissue samples were examined by light and transmission electron microscopy. ResultsThe fasting + PN group exhibited lower insulin levels, higher glucose levels, and increased systemic oxidative stress than the other groups. Ultra-structural and histopathological examinations revealed a significant increase in apoptotic activity in this group’s small intestines and a significant decrease in villus length and crypt depth. Severe damage to the intracellular organelles and nuclei of enterocytes was also observed. ConclusionPN combined with starvation appears to cause apoptosis in the small intestine due to oxidative stress and hyperglycaemia with hypoinsulinemia, with destructive effects on small intestine tissue. Adding enteral nutrition to PN may reduce these destructive effects.

Diagnostic utility of trefoil factor families for the early detection of lung cancer and their correlation with tissue expression.

Trefoil factors (TFFs) are upregulated in numerous types of cancer, including those of the breast, the colon, the lung and the pancreas, suggesting their potential utility as biomarkers for screening. In the present study, the clinical relevance of serum or urinary TFFs as biomarkers were comprehensively evaluated and the correlation with TFF expression levels in lung cancer tissue was examined. Serum and urine were collected from 199 patients with lung cancer and 198 healthy individuals. Concentrations of serum and urinary TFF1, TFF2 and TFF3 were measured using ELISA and the potential of TFF levels to discriminate between cancer and non-cancer samples was evaluated. In 100 of the cancer cases, expression of TFF1-3 was analyzed using immunohistochemical staining of paraffin sections. Furthermore, the relationship between TFF levels and clinicopathological factors among these cancer cases was analyzed using immunohistochemistry of tissue specimens, quantified and statistically analyzed. While serum levels of all TFFs measured using ELISA were significantly higher in patients with lung cancer compared with those in healthy individuals, urinary TFFs were lower. Areas under the curve (AUC) of the receiver operating characteristic curves for serum/urinary TFF1, TFF2 and TFF3 were 0.709/0.594, 0.722/0.501 and 0.663/0.665, respectively. Furthermore, the combination of serum TFF1, TFF2, TFF3 and urinary TFF1 and TFF3 demonstrated the highest AUC (0.826). In the clinicopathological analysis, serum TFF1 was higher in the early pathological T-stage (pTis/1/2) compared with the later stage (pT3/4) and TFF2 was higher in the pN0/1 than the pN2 group. With regards to the histological types, urinary TFF1 was higher in squamous cell carcinoma than adenocarcinoma (AC), but TFF2 tended to be higher in AC. Using immunohistochemical analysis, although TFF1 and TFF3 expression showed positive correlation with serum concentrations, TFF2 was inversely correlated. In conclusion, serum and urinary TFF levels are promising predictive biomarkers, and their measurements provide a useful in vivo and non-invasive diagnostic screening tool. In particular, TFF1 and TFF3 could be surrogate markers of clinicopathological profiles of human lung cancer.

Impacts of Cold-Stress Stimulation On Mice Pregnancy.

Animals exposed to cold stress develop hypertension; however, the effects of cold-induced hypertension on pregnancy remain unclear. We therefore, aimed to investigate the impacts of cold-stress stimulation on mice pregnancy. Four groups of mice were used in the study: non-pregnant control group (NN), non-pregnant cold-stress group (NC), pregnant control group (PN) and pregnant cold-stress group (PC). control groups were kept at 25℃, and the cold-stress groups were kept in a room for cold-stress stimulation (4 ± 2℃) for 4 hours (then back to 25℃) every day from the 1st to the 18th day. The blood pressure of the PC was the highest among the four groups, and the hypertensive percentage of the PC was significantly increased. However, plasma angiotensinⅡ levels of the PC were the lowest. The weights of the foetus and placenta in the PC were significantly decreased compared to the PN. More apparent changes in kidneys and placenta were observed in the PC compared to the PN. The blood pressure of pregnant mice showed no difference between the PN and PC groups 50 days after delivery. Intermittent cold-stress stimulation had significantly adverse effects on the pregnant mice, leading to maternal hypertension, renal and placental lesions, body weight and placenta reduction in offspring. The study results may offer a non-invasive method to establish an animal model of hypertensive disorders in pregnancy. Cold-stress stimulation may be one of the inducible factors of pregnancy-induced hypertension.Cold-stress stimulation may be one of the inducible factors of pregnancy-induced hypertension.

Protective effect of Qingluotongbi formula against Tripterygium wilfordii induced liver injury in mice by improving fatty acid β-oxidation and mitochondrial biosynthesis

Context Qingluotongbi formula (QLT) is a Chinese medicine compound consisting of Tripterygium wilfordii Hook. f. (Celastraceae, TW), Panax notoginseng (Burkill) F.H.Chen (Araliaceae, PN), Rehmannia glutinosa (Gaertn.) DC. (Orobanchaceae, RG), Sinomenium acutum (Thunb.) Rehder & E.H. Wilson (Menispermaceae, SA), and Bombyx mori L. (Bombycidae, BM). Objective This study investigated the protective effect and possible mechanism of QLT against TW-induced liver injury in mice. Materials and methods To establish the model of TW-induced liver injury in mice, C57BL/6J mice were randomly divided into 4 groups: control group, low-dose TW group, middle-dose TW group, and high-dose TW group. To observe the effects of QLT and its individual ingredients against TW-induced liver injury, C57BL/6J mice were randomly divided into 7 groups: control group, TW group, QLT group, PN group, RG group, SA group, BM group. After administration for 7 days, C57BL/6J mice were tested for biochemical indicators and liver pathological changes. Then, we evaluated the mitochondrial function and analysed the gene and protein expression related to the peroxisome proliferator-activated receptor alpha (PPARα)/peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) pathway by quantitative real-time PCR (qRT-PCR) and Western blotting. Results Compared with the control group (0.30 ± 0.35), TW significantly increased mice liver histological score (L, 0.95 ± 1.14; M, 1.25 ± 1.16; H, 4.00 ± 1.13). QLT and its ingredients significantly improved the pathology scores (CON, 0.63 ± 0.74; TW, 4.19 ± 1.53; QLT, 1.56 ± 0.62; PN, 1.94 ± 0.68; RG, 2.75 ± 1.39; SA, 4.13 ± 0.99; BM, 4.13 ± 0.99). Western blot and qRT-PCR analysis revealed that QLT and its ingredients reversed TW-induced suppression of PPARα/PGC1-α pathway. Discussion and conclusions: These findings provide valuable information for compound compatibility studies and TW clinical applications.

Prognostic value of tumour contour irregularity on surgical strategies for T1bN0M0 renal cell carcinoma: A multi-institutional study

PurposeTo determine the prognostic value of tumour contour irregularity degree (CID) in surgical strategy options for T1bN0M0 renal cell carcinoma (RCC). Materials and methodsWe performed a retrospective multi-institutional review of 489 patients with T1bN0M0 RCC treated between January 2009 and June 2019. Cox regression and Kaplan-Meier analyses were performed to analyse the impact of CID on disease-free survival (DFS). ResultsThe median follow-up time was 55 months (interquartile range, 40–81 months) for 55 (11.2 %) patients with metastasis or recurrence. Logistic analysis indicated that CID was associated with World Health Organization/International Society of Urological Pathology (WHO/ISUP) grades III–IV (odds ratio, 1.015; 95 % confidence interval [CI], 1.008–1.023; p < 0.001). After being classified into high CID (≥50 %) and low CID (<50 %) groups, those with a high CID showed a significantly higher ratio of WHO/IUSP grades III–IV (74/277 [26.7 %] vs 25/212 [11.8 %]) and shorter DFS than the low CID group (p < 0.001). Multivariable Cox regression showed that partial nephrectomy (PN; hazard ratio [HR], 1.889; 95 % CI, 1.020–3.499; p = 0.043), high CID (HR, 6.685; 95 % CI, 2.776–16.100; p < 0.001), and WHO/ISUP grade III–IV (HR, 1.950; 95 % CI, 1.100–3.458; p = 0.022) were independent prognostic factors for DFS. The Kaplan-Meier plot showed that PN had a DFS rate comparable to that of radical nephrectomy (RN; p = 0.994). In the low CID group, patients who underwent PN showed comparable DFS to those who underwent RN (p = 0.903). Furthermore, patients with a high CID tended to have worse DFS in the PN versus RN group (p = 0.044). Multivariable Cox regression showed that PN (HR, 2.049; 95 % CI, 1.065–3.942; p = 0.032) and WHO/ISUP grade III–IV (HR, 2.148; 95 % CI, 1.189–3.881; p = 0.011) were independent prognostic factors of DFS in the high CID group. ConclusionsCID is a reliable preoperative parameter which is positively correlated with WHO/ISUP grade and can help with surgical decision-making in patients with T1bN0M0 RCC.

The prognostic impact of lymph node dissection for clinically node-negative upper urinary tract urothelial carcinoma in patients who are treated with radical nephroureterectomy.

To evaluate the prognostic impact of lymph node dissection (LND) in patients who underwent radical nephroureterectomy (RNU) with bladder cuff excision (BCE) for clinically node-negative (cN0) upper urinary tract urothelial carcinoma (UTUC). We retrospectively enrolled 520 patients with cN0 UTUC in a single tertiary referral center from 2000 to 2015. The patients were divided into three groups: patients with and without pathologically proved lymph node metastasis (pN1-3 and pN0, respectively) and patients without LND (pNx). We analyzed associations between overall survival (OS)/ disease-free survival (DFS)/ cancer-specific survival (CSS) and clinical characteristics. The patients were divided into three groups (pN1-3, pN0 and pNx with 20, 303, and 197 patients, respectively). OS/DFS/CSS in the pN1-3 group were significantly worse (all p<0.001) compared with the pN0 group. However, there were no significant differences between the pNx and pN0 groups. In the multivariate analyses, CSS was only affected by age [(hazard ratio (HR) = 1.03, p = 0.008]), positive surgical margin (HR = 3.38, p<0.001) and pathological T3-4 stages (HR = 4.07, p<0.001). In the subgroup analyses for patients with LND, locally advanced disease (pT3 and pT4) had significantly more metastases [T3-4: 13.91% (16/115) vs. T0-2: 1.92% (4/208), p<0.001]. In the pN0 group, LND for cN0 UTUC did not show therapeutic benefits in terms of DFS, CSS, and OS. However, LND with RNU allowed optimal tumor staging, through patients still had a poor prognosis. Clinically occult LN metastases were found in 6.2% of our patients.